In the non-blinded non-randomized phase, overall less AEOIs were reported compared to the blinded phase. However, muscle-related AEOIs were reported more often in statin users than non-users (HR 1.41, 95% CI 1.10-1.79, P=0.006), which proportional excess was similar between atorvastatin- or placebo-assigned patients of blinded phase (P interaction=0.63).

Conclusion

In the blinded randomized phase of the ASCOT-LLA trial, the number of muscle-related AEs were comparable between statin-treated and placebo-treated patients. However, these AEs were significantly more often reported when these same patients knew that they were taking a statin during the extended non-blinded non-randomized phase. This observation is consistent with a nocebo effect, whereby subjective AEs are probably a result of a treatment thought that causes some particular side-effects. These data suggest that muscle-related AEOIs are not causally related to statin-use and therefore, the benefits of statins in reducing cardiovascular events should override concerns about reports of side-effects.